The human and mouse protective protein/cathepsin A (PPCA) genes are highly homologous, both in sequence and organization. Their expression in mammalian tissues is ubiquitous but differential. The mouse gene is transcribed from two promoters, giving rise to two mRNAs which differ in size and tissue distribution. The less abundant, larger transcript of 2.0 kb is present only in a few tissues and is transcribed from a tissue-specific promoter, upstream of the constitutive promoter present in both the human and mouse genes. Northern blot hybridizations demonstrated that these two mRNAs differed only in their 5′UTRs.
PPCA is a lysosomal carboxypeptidase that is deficient in the human lysosomal storage disease galactosialidosis (reviewed in d'Azzo et al., In The Metabolic and Molecular Bases of Inherited Disease, C. Scriver et al. (eds.), New York: McGraw-Hill Publishing Co., pp. 2825-38, 1995). The human and mouse PPCA cDNAs are 85% homologous in their coding regions and 72% identical in the 3′ untranslated regions (Galjart, et al., Cell, 54:755-764, 1988; Galjart, et al., J. Biol. Chem., 265:4678-84, 1990). The genomic organization and structure of the two PPCA genes are also conserved. The human gene maps to chromosome 20q13.1 and the mouse to the syntenic region of chromosome 2-H4 (Wiegant, et al., Genomics, 10:345-349, 1991; Williamson, et al., Genomics, 22:240-242, 1994; Shimmoto, et al., Biochem. Biophys. Res. Comm., 220:802-806, 1996; Rottier and d'Azzo, DNA Cell Biol., 16:599-610, 1997). Shimmoto, et al. showed that the last exon of the human gene, exon XV, partially overlaps over a stretch of 58 nucleotides (nt) with the gene encoding the phospholipid transfer protein (PLTP; Shimmoto, et al., supra). Similarly, the murine PPCA and PLTP genes are in close vicinity and probably overlap as well. Whether these two genes share common regulatory elements is unknown at the moment.